Microfluidic devices and methods are of significant and increasing importance in biomedical and pharmaceutical research. However, considerable challenges remain in applying microfluidic technology to sequential syntheses of fine chemicals and pharmaceuticals. Continuous flow microreactors have recently been used to manipulate individual chemical processes on nanoliter (nL) to microliter (μL) scales with advantages of enhanced heat transfer performance, faster diffusion times and reaction kinetics, and improved reaction product selectivity (de Mello et al., 2002, Lab on a Chip 2:7n; Kikutani and Kitamori, 2004, Macromolecular Rapid Communications 25:158; Jahnisch et al., 2004, Angewandte Chemie-International Edition 43:406; Fletcher et al., 2002, Tetrahedron 58:4735; Worz et al., 2001, Chemical Engineering Science 56, 1029; Watts et al. 2003, Current Opinion in Chemical Biology 7:380). However, in multi-step procedures, flow-through systems are plagued by cross contamination of reagents from different steps; side reactions and poor overall yield result from the inability to confine each individual step. Improved methods and devices are needed.
A compelling application for microfluidic synthesis is in the preparation of organic compounds bearing short-lived isotopes, whose emission permits detailed mapping of biological processes in living organs. See Phelps, 2000, Proc. Nat. Acad. Sci. USA 97: 9226. The development of sensitive radiolabeled molecular probes is crucial for expanding the capability of target-specific in vivo imaging for biological research and drug discovery. The United States already has a vast network of PET cyclotron production sites in place as convenient sources for radiolabeled precursors (e.g., [18F]fluoride, [11C]CO2 and [11C]MeI) and a few labeled biomarkers. The capacity for diversifying radiolabeled probe structure is therefore limited only by the cost, speed, and efficiency of synthetic methods. A microfluidic device that could be used for synthesis of radiopharmaceuticals would constitute a significant advance in medicine and would provide immediate and significant benefit to patients.